tbuckley/cabot-search huggingface dataset:
Gut microbiome and frailty: insight from genetic correlation and mendelian randomization
Authors: Guanghui Cui, Shaojie Li, Hui Ye, Yao Yang, Xiaofen Jia, Miaomiao Lin, Yingming Chu, Yue Feng, Zicheng Wang, Zongming Shi, Xuezhi Zhang
Journal: Gut Microbes (2023)

Observational studies have shown that the gut microbiome is associated with frailty. However, whether these associations underlie causal effects remains unknown. Thus, this study aimed to assess the genetic correlation and causal relationships between the genetically predicted gut microbiome and frailty using linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR). Summary statistics for the gut microbiome were obtained from a genome-wide association study (GWAS) meta-analysis of the MiBioGen consortium (N = 18,340). Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). We used LDSC and MR analyses to estimate the genetic correlation and causality between the genetically predicted gut microbiome and frailty. Our findings indicate a suggestive genetic correlation between Christensenellaceae R-7 and frailty. Moreover, we found evidence for suggestive causal effects of twelve genus-level gut microbes on frailty using at least two MR methods. There was no evidence of horizontal pleiotropy or heterogeneity in the MR analysis. This study provides suggestive evidence for a potential genetic correlation and causal association between several genetically predicted gut microbes and frailty. More population-based observational studies and animal experiments are required to clarify this association and the underlying mechanisms.
Quantitative Biofabrication Platform for Collagen‐Based Peripheral Nerve Grafts with Structural and Chemical Guidance
Authors: Heran Wang, Yiming Hao, Kai Guo, Lianqing Liu, Bing Xia, Xue Gao, Xiongfei Zheng, Jinghui Huang
Journal: Advanced Healthcare Materials (2023)

Owing to its crucial role in the human body, collagen has immense potential as a material for the biofabrication of tissues and organs. However, highly refined fabrication using collagen remains difficult, primarily because of its notably soft properties. A quantitative biofabrication platform to construct collagen-based peripheral nerve grafts, incorporating bionic structural and chemical guidance cues, is introduced. A viscoelastic model for collagen, which facilitates simulating material relaxation and fabricating collagen-based neural grafts, achieving a maximum channel density similar to that of the native nerve structure of longitudinal microchannel arrays, is established. For axonal regeneration over considerable distances, a gradient printing control model and quantitative method are developed to realize the high-precision gradient distribution of nerve growth factor required to obtain nerve grafts through one-step bioprinting. Experiments verify that the bioprinted graft effectively guides linear axonal growth in vitro and in vivo. This study should advance biofabrication methods for a variety of human tissue-engineering applications requiring tailored cues.
Biomimetic Corneal Stroma for Scarless Corneal Wound Healing via Structural Restoration and Microenvironment Modulation
Authors: Jianan Huang, Tuoying Jiang, Jinying Li, Jiqiao Qie, Xiaoyu Cheng, Yiyao Wang, Tinglian Zhou, Jia Liu, Haijie Han, Ke Yao, Luyang Yu
Journal: Advanced Healthcare Materials (2023)

Abstract Corneal injury‐induced stromal scarring causes the most common subtype of corneal blindness, and there is an unmet need to promote scarless corneal wound healing. Herein, a biomimetic corneal stroma with immunomodulatory properties is bioengineered for scarless corneal defect repair. First, a fully defined serum‐free system is established to derive stromal keratocytes (hAESC‐SKs) from a current Good Manufacturing Practice (cGMP)‐grade human amniotic epithelial stem cells (hAESCs), and RNA‐seq is used to validate the phenotypic transition. Moreover, hAESC‐SKs are shown to possess robust immunomodulatory properties in addition to the keratocyte phenotype. Inspired by the corneal stromal extracellular matrix (ECM), a photocurable gelatin‐based hydrogel is fabricated to serve as a scaffold for hAESC‐SKs for bioengineering of a biomimetic corneal stroma. The rabbit corneal defect model is used to confirm that this biomimetic corneal stroma rapidly restores the corneal structure, and effectively reshapes the tissue microenvironment via proteoglycan secretion to promote transparency and inhibition of the inflammatory cascade to alleviate fibrosis, which synergistically reduces scar formation by ≈75% in addition to promoting wound healing. Overall, the strategy proposed here provides a promising solution for scarless corneal defect repair.
Self‐Assembled Acid‐Responsive Nanosystem for Synergistic Anti‐Angiogenic/Photothermal/Ferroptosis Therapy against Esophageal Cancer
Authors: Xiaokun Li, Jiamei Li, Siqin He, Siyuan Luan, Haowen Zhang, Yushang Yang, Xiaoting Chen, Yilong Chen, Jianfeng Zhou, Pinhao Fang, Xin Xiao, Zhiwen Liang, Xiaoxi Zeng, Huile Gao, Yong Yuan
Journal: Advanced Healthcare Materials (2023)

Abstract Esophageal cancer (EC) treatment via anti‐angiogenic therapy faces challenges due to non‐cytotoxicity and non‐specific biodistribution of the anti‐angiogenic agents. Hence, the quest for a synergistic treatment modality and a targeted delivery approach to effectively address EC has become imperative. In this study, an acid‐responsive release nanosystem (Bev‐IR820@Fe III TA) that involves the conjugation of bevacizumab, an anti‐angiogenic monoclonal antibody, with TA and Fe 3+ to form a metal‐phenolic network, followed by loading with the near‐infrared photothermal agent (IR820) to achieve combinational therapy, is designed. The construction of Bev‐IR820@Fe III TA can be realized through a facile self‐assembly process. The Bev‐IR820@Fe III TA exhibits tumor‐targeting capabilities and synergistic therapeutic effects, encompassing anti‐angiogenic therapy, photothermal therapy (PTT), and ferroptosis therapy (FT). Bev‐IR820@Fe III TA exhibits remarkable proficiency in delivering drugs to EC tissue through its pH‐responsive release properties. Consequently, bevacizumab exerts its therapeutic effects by obstructing tumor angiogenesis, thereby impeding tumor growth. Meanwhile, PTT facilitates localized thermal ablation at the tumor site, directly eradicating EC cells. FT synergistically collaborates with PTT, giving rise to the formation of a reactive oxygen species (ROS) storm, subsequently culminating in the demise of EC cells. In summary, this amalgamated treatment modality carries substantial promise for synergistically impeding EC progression and showcases auspicious prospects for future EC treatment.
The B1 H+-ATPase (Atp6v1b1) Subunit in Non–Type A Intercalated Cells is Required for Driving Pendrin Activity and the Renal Defense Against Alkalosis
Authors: Soline Bourgeois, Jana Kovacikova, Milica Bugarski, Carla Bettoni, Nicole Gehring, Andrew Hall, Carsten A. Wagner
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement In the kidney, the B1 H + -ATPase subunit is mostly expressed in intercalated cells (IC). Its importance in acid-secreting type A ICs is evident in patients with inborn distal renal tubular acidosis and ATP6V1B1 mutations. However, the protein is also highly expressed in alkali-secreting non–type A ICs where its function is incompletely understood. We demonstrate in Atp6v1b1 knock out mice that the B1 subunit is critical for the renal response to defend against alkalosis during an alkali load or chronic furosemide treatment. These findings highlight the importance of non–type A ICs in maintaining acid–base balance in response to metabolic challenges or commonly used diuretics. Background Non–type A ICs in the collecting duct system express the luminal Cl − /HCO 3 − exchanger pendrin and apical and/or basolateral H + -ATPases containing the B1 subunit isoform. Non–type A ICs excrete bicarbonate during metabolic alkalosis. Mutations in the B1 subunit (ATP6V1B1) cause distal renal tubular acidosis due to its role in acid secretory type A ICs. The function of B1 in non–type A ICs has remained elusive. Methods We examined the responses of Atp6v1b1 −/− and Atp6v1b1 +/+ mice to an alkali load and to chronic treatment with furosemide. Results An alkali load or 1 week of furosemide resulted in a more pronounced hypokalemic alkalosis in male ATP6v1b1 −/− versus Atp6v1b1 +/+ mice that could not be compensated by respiration. Total pendrin expression and activity in non–type A ICs of ex vivo microperfused cortical collecting ducts were reduced, and β 2 -adrenergic stimulation of pendrin activity was blunted in ATP6v1b1 −/− mice. Basolateral H + -ATPase activity was strongly reduced, although the basolateral expression of the B2 isoform was increased. Ligation assays for H + -ATPase subunits indicated impaired assembly of V 0 and V 1 H + -ATPase domains. During chronic furosemide treatment, ATP6v1b1 −/− mice also showed polyuria and hyperchloremia versus Atp6v1b1 +/+ . The expression of pendrin, the water channel AQP2, and subunits of the epithelial sodium channel ENaC were reduced. Conclusions Our data demonstrate a critical role of H + -ATPases in non–type A ICs function protecting against alkalosis and reveal a hitherto unrecognized need of basolateral B1 isoform for a proper H + -ATPase complexes assembly and ability to be stimulated.
Alendronate Pt<sup>IV</sup> Prodrug Amphiphile for Enhanced Chemotherapy Targeting and Bone Destruction Inhibition in Osteosarcoma
Authors: Kaichuang Sun, Lu Yuan, Shen Chen, Yong Sun, Dengshuai Wei
Journal: Advanced Healthcare Materials (2023)

Abstract Chemotherapy remains the primary treatment method for osteosarcoma after surgery. However, the lack of selectivity of chemotherapy for osteosarcoma leads to unpredictable therapeutic effects, undesirable side effects, and drug resistance. A platinum(IV) (Pt IV ) prodrug amphiphile (ALN‐Pt IV ‐Lipo) covalently bound to alendronate (ALN) and a lipid tail is designed to overcome these limitations. ALN‐Pt IV ‐Lipo can self‐assemble into Pt IV lipid nanoparticles (APt IV ) for osteosarcoma targeting chemotherapy and bone destruction inhibition. It is demonstrated that APt IV achieved an eightfold increase in the eradication of osteosarcoma cells compared to cisplatin and threefold selective inhibition of osteosarcoma cells over breast cancer cells via APt IV in vitro. After intravenous injection, APt IV effectively accumulates at the osteosarcoma site in vivo, resulting in significantly suppressed primary osteosarcoma growth, and alleviation of bone destruction. Therefore, APt IV delivers a promising solution for enhanced chemotherapy targeting and bone destruction inhibition in osteosarcoma.
Educating the healthcare workforce of the future: lessons learned from the development and implementation of a ‘Wearables in Healthcare’ course
Authors: Matthew P. Ward, J. Scott Malloy, Chris Kannmacher, Steven R. Steinhubl
Journal: npj Digital Medicine (2023)

Abstract Digital health technologies will play an ever-increasing role in the future of healthcare. It is crucial that the people who will help make that transformation possible have the evidence-based and hands-on training necessary to address the many challenges ahead. To better prepare the future health workforce with the knowledge necessary to support the re-engineering of healthcare in an equitable, person-centric manner, we developed an experiential learning course—Wearables in Healthcare—for advanced undergraduate and graduate university students. Here we describe the components of that course and the lessons learned to help guide others interested in developing similar courses.
Subclinical inflammation and joint damage progression in patients with early RA fulfilling 2011 vs 2022 ACR/EULAR Boolean remission criteria: data from the ARCTIC study
Authors: Valeriia Melokhina, Nina Paulshus Sundlisæter, Joseph Sexton, Ulf Sundin, Anna-Birgitte Aga, Kaja E Kjørholt, Lena Bugge Nordberg, Désirée van der Heijde, Espen Haavardsholm, Siri Lillegraven
Journal: Annals of the Rheumatic Diseases (2023)

Patients on a bDMARD †, n (%) 15 ( 14) 3 ( 12) 15 (13) 3 (20) NA NA *Mean difference based on the linear mixed model with both 12-month and 24-month data.†All bDMARDs were TNF-alfa inhibitors.bDMARDs, biological disease-modifying antirheumatic drugs; DAS,
Bioactive Conjugated Polymer‐Based Biodegradable 3D Bionic Scaffolds for Facilitating Bone Defect Repair
Authors: Qiong Yuan, Benkai Bao, Meiqi Li, Ling Li, Xinyi Zhang, Yanli Tang
Journal: Advanced Healthcare Materials (2023)

Abstract Bone defect regeneration is one of the great clinical challenges. Suitable bioactive composite scaffolds with high biocompatibility, robust new‐bone formation capability and degradability are still required. This work designs and synthesizes an unprecedented bioactive conjugated polymer PT‐C 3 ‐NH 2 , demonstrating low cytotoxicity, cell proliferation/migration‐promoting effect, as well as inducing cell differentiation, namely regulating angiogenesis and osteogenesis to MC3T3‐E1 cells. PT‐C 3 ‐NH 2 is incorporated into polylactic acid‐glycolic acid (PLGA) scaffolds, which is decorated with caffeic acid (CA)‐modified gelatin (Gel), aiming to improve the surface water‐wettability of PLGA and also facilitate to the linkage of conjugated polymer through catechol chemistry. A 3D composite scaffold PLGA@GC‐PT is then generated. This scaffold demonstrates excellent bionic structures with pore size of 50–300 µm and feasible biodegradation ability. Moreover, it also exhibites robust osteogenic effect to promote osteoblast proliferation and differentiation in vitro, thus enabling the rapid regeneration of bone defects in vivo. Overall, this study provides a new bioactive factor and feasible fabrication approach of biomimetic scaffold for bone regeneration.
Delivery of mRNA Vaccine with 1, 2‐Diesters‐Derived Lipids Elicits Fast Liver Clearance for Safe and Effective Cancer Immunotherapy
Authors: Yuandong Xu, Yuexiao Hu, Heng Xia, Shiqiang Zhang, Hanqi Lei, Binyuan Yan, Ze Xiu Xiao, Jinjin Chen, Jun Pang, Gao‐Feng Zha
Journal: Advanced Healthcare Materials (2023)

Messenger RNA (mRNA) vaccine is explored as a promising strategy for cancer immunotherapy, but the side effects, especially the liver-related damage caused by LNP, raise concerns about its safety. In this study, a novel library of 248 ionizable lipids comprising 1,2-diesters is designed via a two-step process involving the epoxide ring-opening reaction with carboxyl group-containing alkyl chains followed by an esterification reaction with the tertiary amines. Owing to the special chemical structure of 1,2-diesters, the top-performing lipids and formulations exhibit a faster clearance rate in the liver, contributing to increased stability and higher safety compared with DLin-MC3-DMA. Moreover, the LNP shows superior intramuscular mRNA delivery and elicits robust antigen-specific immune activation. The vaccinations delivered by the LNP system suppress tumor growth and prolong survival in both model human papillomavirus E7 and ovalbumin antigen-expressing tumor models. Finally, the structure of lipids which enhances the protein expression in the spleen and draining lymph nodes compared with ALC-0315 lipid in Comirnaty is further optimized. In conclusion, the 1, 2-diester-derived lipids exhibit rapid liver clearance and effective anticancer efficiency to different types of antigens-expressing tumor models, which may be a safe and universal platform for mRNA vaccines.
Right Atrial Angiosarcoma with Embolic Lung Metastases Masquerading as Atypical Pneumonitis
Authors: Chung-Fu Lin, Yu-Wei Wu, Wei-An Liao, Chia-Ying Lin, Ying-Tzu Huang, Tang-Hsiu Huang
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Right Atrial Angiosarcoma with Embolic Lung Metastases Masquerading as Atypical Pneumonitis." American Journal of Respiratory and Critical Care Medicine, 209(3), pp. 325–328
Impact of vasodilators on diuretic response in patients with congestive heart failure: A mechanistic trial of cimlanod (<scp>BMS</scp>‐986231)
Authors: Pierpaolo Pellicori, John G.F. Cleland, Maria Borentain, Jorg Taubel, Fraser J. Graham, Javed Khan, Dario Bruzzese, Paul Kessler, John J.V. McMurray, Adriaan A. Voors, Christopher M. O'Connor, John R. Teerlink, G. Michael Felker
Journal: European Journal of Heart Failure (2023)

Aim To investigate the effects of Cimlanod, a nitroxyl donor with vasodilator properties, on water and salt excretion after an administration of an intravenos bolus of furosemide. Methods and results In this randomized, double‐blind, mechanistic, crossover trial, 21 patients with left ventricular ejection fraction &lt;45%, increased plasma concentrations of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and receiving loop diuretics were given, on separate study days, either an 8 h intravenous (IV) infusion of cimlanod (12 μg/kg/min) or placebo. Furosemide was given as a 40 mg IV bolus four hours after the start of infusion. The primary endpoint was urine volume in the 4 h after the bolus of furosemide during infusion of cimlanod compared with placebo. Median NT‐proBNP at baseline was 1487 (interquartile range: 847–2665) ng/L. Infusion of cimlanod increased cardiac output and reduced blood pressure without affecting cardiac power index consistent with its vasodilator effects. Urine volume in the 4 h post‐furosemide was lower with cimlanod (1032 ± 393 ml) versus placebo (1481 ± 560 ml) ( p = 0.002), as were total sodium excretion ( p = 0.004), fractional sodium excretion ( p = 0.016), systolic blood pressure ( p &lt; 0.001), estimated glomerular filtration rate ( p = 0.012), and haemoglobin ( p = 0.010), an index of plasma volume expansion. Conclusions For patients with heart failure and congestion, vasodilatation with agents such as cimlanod reduces the response to diuretic agents, which may offset any benefit from acute reductions in cardiac preload and afterload.
Introducing Specific Iodine Ions in Perovskite‐Based Nanocomplex to Cater for Versatile Biomedical Imaging and Tumor Radiotherapy
Authors: Yumeng Yue, Haoran Xu, Liwen Jiang, Xiaomin Zhao, Dawei Deng
Journal: Advanced Healthcare Materials (2023)

Abstract Multimodal biomedical imaging and imaging‐guided therapy have garnered extensive attention owing to the aid of nanoagents with the aim of further improving the therapeutic efficacy of diseases. The ability to engineer nanocomplexes (NCs) or control how they behave within an organism remains largely elusive. Here, a multifunctional nanoplatform is developed based on stabilized I‐doped perovskite, CsPbBr 3 ‐x I x @SiO 2 @Lip‐c(RGD) 2 (PSL‐c(RGD) 2 ) NCs. In particular, by regulating the amount of regular I − ions introduced, the fluorescence emission spectrum of perovskite‐based NCs can be modulated well to match the requirement for biomedical optical imaging at the scale from molecule, cell to mouse; doping 125 I enables the nanoformulation to be competent for single‐photon emission computed tomography (SPECT) imaging; the introduction of 131 I − imparts the NCs with the capability for radiotherapy. Through facile manipulation of specific iodine ions, this nanoplatform exhibits a remarkable ability to match multifunctional biomedical imaging and tumor therapy. In addition, their in vivo behavior can be manipulated by adjusting the thickness of the silica shell and the surface polarity for more practical applications. These experimental explorations offer a novel approach for engineering desirable multimodal NCs to simultaneously image and combat malignant tumors.
High‐Resolution Additive Manufacturing of a Biodegradable Elastomer with A Low‐Cost LCD 3D Printer
Authors: Vahid Karamzadeh, Molly L. Shen, Hossein Ravanbakhsh, Ahmad Sohrabi‐Kashani, Sargol Okhovatian, Houman Savoji, Milica Radisic, David Juncker
Journal: Advanced Healthcare Materials (2023)

Artificial organs and organs-on-a-chip (OoC) are of great clinical and scientific interest and have recently been made by additive manufacturing, but depend on, and benefit from, biocompatible, biodegradable, and soft materials. Poly(octamethylene maleate (anhydride) citrate (POMaC) meets these criteria and has gained popularity, and as in principle, it can be photocured and is amenable to vat-photopolymerization (VP) 3D printing, but only low-resolution structures have been produced so far. Here, a VP-POMaC ink is introduced and 3D printing of 80 µm positive features and complex 3D structures is demonstrated using low-cost (≈US$300) liquid-crystal display (LCD) printers. The ink includes POMaC, a diluent and porogen additive to reduce viscosity within the range of VP, and a crosslinker to speed up reaction kinetics. The mechanical properties of the cured ink are tuned to match the elastic moduli of different tissues simply by varying the porogen concentration. The biocompatibility is assessed by cell culture which yielded 80% viability and the potential for tissue engineering illustrated with a 3D-printed gyroid seeded with cells. VP-POMaC and low-cost LCD printers make the additive manufacturing of high resolution, elastomeric, and biodegradable constructs widely accessible, paving the way for a myriad of applications in tissue engineering and 3D cell culture as demonstrated here, and possibly in OoC, implants, wearables, and soft robotics.
John Launer: Reflective writing and feeding the monster
Authors: John Launer
Journal: BMJ (2023)

Reflection is all the rage.Medical students are asked to write reflections on their encounters with patients.Junior doctors in some specialties have to enter these in their electronic portfolios.The documents we have to fill in for our annual appraisals include space for written reflections on the year's achievements.In some circumstances-for example, with significant events or complaints-these may be compulsory.Who could possibly object?No patient wants to be seen by a doctor who is unreflective.The ability to examine one's thoughts and emotions, and to write about them and learn more by doing so, is arguably a core professional attribute.Personally, I confess to a liking for the habit.
Cirrhosis in over 16s: assessment and management—updated summary of NICE guidance
Authors: Chris Carmona, Lindsay Claxton, Alastair O’Brien, Vanessa Hebditch
Journal: BMJ (2023)

### What you need to know Liver cirrhosis affects 110 people per 100 000 in the UK1 and is closely linked with deprivation. The British Liver Trust2 estimates premature deaths from liver disease to be four times higher in the most deprived areas compared with the most affluent. Early identification and management can delay decompensation events such as variceal bleeding, ascites, and hepatic encephalopathy, leading to longer, better quality life for people with liver disease. In 2015, the National Institute for Health and Care Excellence (NICE) first published guidance on the assessment and early management of cirrhosis in people over 16. This article summarises updated 2023 recommendations, focusing on managing complications, and appraises new evidence related to the effectiveness of non-selective beta blockers (NSBBs) for the primary prevention of decompensation in people with cirrhosis.3 The new guidance also updates recommendations about prevention of variceal bleeding in people with cirrhosis and medium or large oesophageal varices, and the primary prevention of spontaneous bacterial peritonitis in people with cirrhosis and ascites. NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the guideline committee’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italics in square brackets. Definitions of evidence certainty are given in box 1. Box 1 ### GRADE Working Group grades of evidenceRETURN TO TEXT